Leukocyte Ig‐Like receptor B1 restrains dendritic cell function through increased expression of the NF‐κB regulator ABIN1/TNIP1

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: LILRB1;    immunosuppression;    lymphoma;    DC maturation;    inhibitory receptor;   

DOI  :  10.1189/jlb.1A0915-420RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inhibitoryreceptorsofthehumanleukocyteimmunoglobulin‐likereceptorfamilyareconstitutivelyexpressedonallmyeloidcelltypesandregulatetheirfunctionalactivity.WedemonstratethatligationofthehumanleukocyteantigenclassI‐specificreceptorLILRB1,duringthedifferentiationofmonocytestodendriticcellsinvitro,resultsinincreasedexpressionofthenuclearfactorκBinhibitorproteinABIN1(alsoknownasTNIP1).SimilarlyincreasedexpressionofABIN1/TNIP1wasobservedinthe“immunosuppressive”monocytepopulationsofpatientswithnon–Hodgkinlymphomaexvivo.ReducingexpressionofABIN1/TNIP1usingsmallinterferingribonucleicacidallowsdendriticcellsandimmunosuppressivemonocytestorespondtostimulationbyallowingnuclearfactorκBtranslocationtothenucleus(P<0.001),increasingcellsurfaceexpressionofantigenpresentationandcostimulatorymolecules(P<0.01),increasingphagocyticcapacity(P<0.001),secretingproinflammatorycytokines(P<0.01),andanincreasingabilitytostimulateTcellresponses(P<0.05).Ourstudy,therefore,identifiesanimportantfunctionalroleforABIN1/TNIP1inmediatingtheeffectsofLILRB1ligation‐inducedinhibitoryeffectsonimmuneresponses.OurfindingssuggestthatinhibitingtheLILRB1‐ABIN1/TNIP1pathwayinantigen‐presentingcellscouldbeatherapeuticapproachtostimulateantitumorimmuneresponses.Conversely,stimulationofthepathwaymayalsoameliorateautoimmunediseasesinwhichTNIP1isasusceptibilitygene...

【 授权许可】

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